In pediatric oncology, managing infections like varicella (chickenpox) and measles is crucial due to the patients’ compromised immune systems. Prevention strategies are paramount and include hygiene measures, isolation protocols, and vaccinations. Treatment is tailored to the specific infection and the patient’s immunological status, often involving antiviral, antibacterial, or antifungal agents, and supportive care. Monitoring for early signs of infection and prompt intervention are key components of care in this vulnerable population.
Varicella zoster
Varicella zoster virus (VZV) is a human alpha herpesvirus, which causes varicella (chicken pox) as the primary infection; VZV then establishes latency and re-activates to cause herpes zoster (shingles). Varicella can be life threatening in children with cancer, and infection is associated with cancer treatment delays.
Ask about a history of clinical varicella in the patient and household contacts at diagnosis and arrange vaccination of household contacts with a negative history of chickenpox. Pre-transfusion VZV antibody status should be checked on all patients at the time of diagnosis and should be recorded in the parent held record.
Special circumstances occur after autologous or allogeneic HSCT where the child should be considered at risk irrespective of VZV antibody status until at least 2 years post HSCT and at least 12 months off all immunosuppressive therapy. This should be guided by the BMT team.
Vaccination of siblings/household contacts
Exposure within the household is the setting most likely to cause varicella in the immunocompromised child. It is recommended that healthy susceptible close household contacts of immunocompromised patients receive the VZV vaccine; household contacts that are over one year of age and without clinical history of chicken pox should be vaccinated. The small risk of vaccine related varicella (usually within 1 month of vaccination) should be discussed with the patient and parents. If vaccine related varicella does occur in the vaccine recipient, give the immunocompromised patient prophylactic VZIG.
Post exposure prophylaxis
Patients receiving standard-dose chemotherapy and up to 6 months after receiving standard dose chemotherapy and following HSCT are at risk of developing varicella following a significant
VZV exposure.
If urgent VZV antibody testing is required for patients presenting late, VZIG can be ordered at the same time that the blood is sent for testing and can be returned if the result is positive. If there is significant exposure and VZV status is unknown, send a blood sample to check VZV serostatus. It is usually necessary to recheck VZV serostatus of VZV antibody negative patients with a significant exposure before VZIG is released. However, VZIG administration should not be delayed past 7 days after initial exposure while an antibody test is done. Under these circumstances VZIG should be given on the basis of a negative history of varicella.
For the group of patients with a positive VZV IgG at diagnosis, there is evidence to show that this group of patients may become VZV negative whilst on chemotherapy. Subsequently, the VZV IgG may return to positive naturally. If the patient’s VZV IgG serostatus changes from positive (at diagnosis) to negative whilst on chemotherapy, there is currently lack of available evidence to support an increased risk of patients developing clinical VZV infection. Therefore, there is currently insufficient evidence to recommend universal re-testing of VZV status in children who were previously VZV positive.
VZIG is not indicated in immunosuppressed patients with detectable VZV antibody as the amount of antibody provided by VZIG will not significantly increase VZV antibody titers in those who are already antibody positive.
Varicella can occasionally occur in immunosuppressed VZV antibody positive patients, but these are likely to be related to defects in cell-mediated immunity.
At risk post HCST patients
Haemopoietic stem cell transplant patients are at risk of VZV irrespective of antibody status and should receive VZIG up to 2 years post procedure and up to 12 months off all immunosuppressive therapy, unless on acyclovir or IVIG prophylaxis.
Definition of significant exposure to VZV
Type of VZV infection in index case:
The risk of acquiring infection from an immunocompetent individual with non-exposed zoster lesions is remote. The issue of VZIG should be restricted to those in contact with:
- Varicella
- Disseminated zoster
- Immunocompetent individuals with exposed zoster lesions
- Immunosuppressed patients with localised zoster on any part of body (viral shedding can be greater in immunosuppressed patients)
Timing of exposure in relation to onset of rash in index case:
- Varicella or disseminated zoster – between 48hrs before onset of rash until no new lesions cropping/ crusting of lesions.
- Localised zoster – day of onset of rash until crusting of lesions.
Closeness and duration of contact:
- Play or direct contact (in the same enclosed space such as house, classroom or 2/4 bedded hospital bay) for ≥15 minutes.
- Face to face contact.
- In the case of large open Paediatric wards/ outpatient department, airborne transmission at a distance has occasionally been reported and giving VZIG to all susceptible high-risk contacts should be considered.
VZIG or alternate treatment
Dose of VZIG:
- 0–5 years, 250mg (one vial)
- 6–10 years, 500mg (two vials)
- 11–14 years, 750mg (three vials)
- 15 years or over, 1000mg (four vials).
- Given by slow IM injection.
Patients with thrombocytopenia/ bleeding disorders who cannot be given an intramuscular injection should be given intravenous normal immunoglobulin (HNIG) at a dose of 0.2g/kg body (i.e. 4ml/kg for a 5% solution) instead. This will produce serum VZ antibody levels equivalent to those achieved with VZIG.
If VZIG is not available, alternatives are:
- HNIG or
- High dose oral acyclovir for 14 days starting at Day 7 after exposure (i.e. from 7-21 days following contact).
Re-exposure
Children re-exposed to varicella or zoster (see above for details of significant exposure) after ≥3 weeks of receiving VZIG and who are VZV IgG negative should have further dose of VZIG.
Treatment of Clinical Varicella/ Herpes Zoster
Varicella and herpes zoster can be fatal in immunosuppressed patients. Presentation may be atypical. Patients should receive intravenous acyclovir for 5 days (or until there are no new lesions developing) followed by 5 days of oral acyclovir (check renal function and modify dose if needed).
If cropping of new lesions continues the IV acyclovir should be given until no lesions develop and crusting of lesions occurs.
Patients who have clinical reactivation of VZV after allogeneic HSCT should continue on acyclovir prophylaxis for a further 3 months.
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